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Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase.

TGF-beta signaling is essential for development and proliferative homeostasis. During embryogenesis, maternal determinants act in concert with TGF-beta signals to form mesoderm and endoderm. In contrast, ectoderm specification requires the TGF-beta response to be attenuated, although the mechanisms by which this is achieved remain unknown. In a functional screen for ectoderm determinants, we have identified Ectodermin (Ecto). In Xenopus embryos, Ecto is essential for the specification of the ectoderm and acts by restricting the mesoderm-inducing activity of TGF-beta signals to the mesoderm and favoring neural induction. Ecto is a RING-type ubiquitin ligase for Smad4, a TGF-beta signal transducer. Depletion of Ecto in human cells enforces TGF-beta-induced cytostasis and, moreover, plays a causal role in limiting the antimitogenic effects of Smad4 in tumor cells. We propose that Ectodermin is a key switch in the control of TGF-beta gene responses during early embryonic development and cell proliferation.

Pubmed ID: 15820681


  • Dupont S
  • Zacchigna L
  • Cordenonsi M
  • Soligo S
  • Adorno M
  • Rugge M
  • Piccolo S



Publication Data

April 8, 2005

Associated Grants

  • Agency: Telethon, Id: GGP04030

Mesh Terms

  • Animals
  • Base Sequence
  • Blastula
  • Bone Morphogenetic Protein Receptors
  • Cell Differentiation
  • Cell Nucleus
  • Cell Proliferation
  • Cells, Cultured
  • Colon
  • Colonic Neoplasms
  • DNA-Binding Proteins
  • Gene Library
  • Germ Layers
  • Humans
  • Molecular Sequence Data
  • Receptors, Growth Factor
  • Signal Transduction
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Ubiquitin-Protein Ligases
  • Xenopus
  • Xenopus Proteins